Diagnosis and Treatment > Signs and Symptoms > Palpitations

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Ohoud Al Mohareb Obesity, Endocrine and Metabolism Centre, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia

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Mussa H Al Malki Obesity, Endocrine and Metabolism Centre, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia

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O Thomas Mueller Department of Pathology and Laboratory Medicine, Molecular and Biochemical Section, All Children Hospital, St Petersburg, Florida, USA

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Imad Brema Obesity, Endocrine and Metabolism Centre, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia

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Summary

Resistance to thyroid hormone-beta (RTHbeta) is a rare inherited syndrome characterized by variable reduced tissue responsiveness to the intracellular action of triiodothyronine (T3), the active form of the thyroid hormone. The presentation of RTHbeta is quite variable and mutations in the thyroid hormone receptor beta (THR-B) gene have been detected in up to 90% of patients. The proband was a 34-year-old Jordanian male who presented with intermittent palpitations. His thyroid function tests (TFTs) showed a discordant profile with high free T4 (FT4) at 45.7 pmol/L (normal: 12–22), high free T3 (FT3) at 11.8 pmol/L (normal: 3.1–6.8) and inappropriately normal TSH at 3.19 mIU/L (normal: 0.27–4.2). Work up has confirmed normal alpha subunit of TSH of 0.1 ng/mL (normal <0.5) and pituitary MRI showed no evidence of a pituitary adenoma; however, there was an interesting coincidental finding of partially empty sella. RTHbeta was suspected and genetic testing confirmed a known mutation in the THR-B gene, where a heterozygous A to G base change substitutes valine for methionine at codon 310. Screening the immediate family revealed that the eldest son (5 years old) also has discordant thyroid function profile consistent with RTHbeta and genetic testing confirmed the same M310V mutation that his father harbored. Moreover, the 5-year-old son had hyperactivity, impulsivity and aggressive behavior consistent with attention deficit hyperactivity disorder (ADHD). This case demonstrates an unusual co-existence of RTHbeta and partially empty sella in the same patient which, to our knowledge, has not been reported before.

Learning points:

  • We report the coincidental occurrence of RTHbeta and a partially empty sella in the same patient that has not been previously reported.

  • TFTs should be done in all children who present with symptoms suggestive of ADHD as RTHbeta is a common finding in these children.

  • The management of children with ADHD and RTHbeta could be challenging for both pediatricians and parents and the administration of T3 with close monitoring may be helpful in some cases.

  • Incidental pituitary abnormalities do exist in patients with RTHbeta, although extremely rare, and should be evaluated thoroughly and separately.

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Carolina Shalini Singarayar Endocrine Unit, Department of Medicine, Selayang Hospital, Selangor, Malaysia

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Foo Siew Hui Endocrine Unit, Department of Medicine, Selayang Hospital, Selangor, Malaysia

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Nicholas Cheong Endocrine Unit, Department of Medicine, Selayang Hospital, Selangor, Malaysia

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Goay Swee En Endocrine Unit, Department of Medicine, Selayang Hospital, Selangor, Malaysia

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Summary

Thyrotoxicosis is associated with cardiac dysfunction; more commonly, left ventricular dysfunction. However, in recent years, there have been more cases reported on right ventricular dysfunction, often associated with pulmonary hypertension in patients with thyrotoxicosis. Three cases of thyrotoxicosis associated with right ventricular dysfunction were presented. A total of 25 other cases of thyrotoxicosis associated with right ventricular dysfunction published from 1994 to 2017 were reviewed along with the present 3 cases. The mean age was 45 years. Most (82%) of the cases were newly diagnosed thyrotoxicosis. There was a preponderance of female gender (71%) and Graves’ disease (86%) as the underlying aetiology. Common presenting features included dyspnoea, fatigue and ankle oedema. Atrial fibrillation was reported in 50% of the cases. The echocardiography for almost all cases revealed dilated right atrial and or ventricular chambers with elevated pulmonary artery pressure. The abnormal echocardiographic parameters were resolved in most cases after rendering the patients euthyroid. Right ventricular dysfunction and pulmonary hypertension are not well-recognized complications of thyrotoxicosis. They are life-threatening conditions that can be reversed with early recognition and treatment of thyrotoxicosis. Signs and symptoms of right ventricular dysfunction should be sought in all patients with newly diagnosed thyrotoxicosis, and prompt restoration of euthyroidism is warranted in affected patients before the development of overt right heart failure.

Learning points:

  • Thyrotoxicosis is associated with right ventricular dysfunction and pulmonary hypertension apart from left ventricular dysfunction described in typical thyrotoxic cardiomyopathy.

  • Symptoms and signs of right ventricular dysfunction and pulmonary hypertension should be sought in all patients with newly diagnosed thyrotoxicosis.

  • Thyrotoxicosis should be considered in all cases of right ventricular dysfunction or pulmonary hypertension not readily explained by other causes.

  • Prompt restoration of euthyroidism is warranted in patients with thyrotoxicosis complicated by right ventricular dysfunction with or without pulmonary hypertension to allow timely resolution of the abnormal cardiac parameters before development of overt right heart failure.

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Catherine Alguire Division of Endocrinology, Department of Medicine and Research Center (CRCHUM), Centre hospitalier de l’Université de Montréal, Montreal, Québec, Canada

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Jessica Chbat Division of Endocrinology, Department of Medicine and Research Center (CRCHUM), Centre hospitalier de l’Université de Montréal, Montreal, Québec, Canada

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Isabelle Forest Department of Psychiatry, Centre hospitalier Pierre-Le Gardeur, Terrebonne, Québec, Canada

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Ariane Godbout Division of Endocrinology, Department of Medicine and Research Center (CRCHUM), Centre hospitalier de l’Université de Montréal, Montreal, Québec, Canada

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Isabelle Bourdeau Division of Endocrinology, Department of Medicine and Research Center (CRCHUM), Centre hospitalier de l’Université de Montréal, Montreal, Québec, Canada

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Summary

Pheochromocytoma is a rare tumor of the adrenal gland. It often presents with the classic triad of headache, palpitations and generalized sweating. Although not described as a typical symptom of pheochromocytoma, anxiety is the fourth most common symptom reported by patients suffering of pheochromocytoma. We report the case of a 64 year old man who had severe anxiety and panic disorder as presenting symptoms of pheochromocytoma. After 13 years of psychiatric follow-up, the patient was diagnosed with malignant pheochromocytoma. After surgical resection of his pheochromocytoma and his hepatic metastases, the major panic attacks completely disappeared, the anxiety symptoms improved significantly and the psychiatric medications were stopped except for a very low maintenance dose of venlafaxine. We found in our cohort of 160 patients with pheochromocytoma 2 others cases of apparently benign tumors with severe anxiety that resolved after pheochromocytoma resection. These cases highlight that pheochromocytoma should be included in the differential diagnosis of refractory anxiety disorder.

Learning points:

  • Anxiety and panic disorder may be the main presenting symptoms of pheochromocytoma.

  • The diagnosis of pheochromocytoma should be excluded in cases of long-term panic disorder refractory to medications since the anxiety may be secondary to a catecholamine-secreting tumor.

  • Surgical treatment of pheochromocytoma leads to significant improvement of anxiety disorders.

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Cheuk-Lik Wong Department of Medicine and Geriatrics, Caritas Medical Centre, Shamshuipo, Kowloon, Hong Kong SAR

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Chun-Kit Fok Department of Medicine and Geriatrics, Caritas Medical Centre, Shamshuipo, Kowloon, Hong Kong SAR

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Vicki Ho-Kee Tam Department of Medicine and Geriatrics, Caritas Medical Centre, Shamshuipo, Kowloon, Hong Kong SAR

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Summary

We report a case of elderly Chinese lady with neurofibromatosis type-1 presenting with longstanding palpitation, paroxysmal hypertension and osteoporosis. Biochemical testing showed mild hypercalcaemia with non-suppressed parathyroid hormone level suggestive of primary hyperparathyroidism, and mildly elevated urinary fractionated normetanephrine and plasma-free normetanephrine pointing to a catecholamine-secreting pheochromocytoma/paraganglioma. Further scintigraphic investigation revealed evidence of a solitary parathyroid adenoma causing primary hyperparathyroidism and a left pheochromocytoma. Resection of the parathyroid adenoma and pheochromocytoma resulted in normalization of biochemical abnormalities and hypertension. The rare concurrence of primary hyperparathyroidism and pheochromocytoma in neurofibromatosis type-1 is discussed.

Learning points:

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V Larouche Resident, Adult Endocrinology and Metabolism Training Program, McGill University, Montréal, Québec, Canada

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M Tamilia Division of Endocrinology, Jewish General Hospital, Montréal, Québec, Canada

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Summary

Enteroviruses, including coxsackieviruses and Echovirus, are well known pathogens responsible for the development of thyroiditis. We describe the case of a 49-year-old woman with no personal or family history of thyroid disease who presented to the emergency room with a two-week history of daily fevers up to 39°C, a sore throat, occasional palpitations and diaphoresis, decreased appetite and an unintentional 10 kg weight loss over the same time course Physical examination revealed mild tachycardia, an intention tremor and a normal-sized, nontender thyroid gland without palpable nodules. The remainder of the physical examination was unremarkable and without stigmata of Graves’ disease. Her initial blood tests revealed overt thyrotoxicosis, elevated liver enzymes, an elevated C-reactive protein, a negative monospot and a positive CMV IgM antibody. Thyroid sonography revealed areas of hypoechogenicity and relatively low vascularity. Fine-needle biopsy showed a lymphocytic infiltrate. The patient was treated symptomatically with propranolol. On follow-up, the patient became euthyroid, and her liver enzymes normalised. Previous cases of CMV-induced thyroiditis occurred in immunosuppressed patients. This is the first reported case of a CMV-mononucleosis-induced thyroiditis in an immunocompetent adult patient and serves as a reminder that viral illnesses are a common cause of thyroiditis with abnormal liver enzymes.

Learning points:

  • The differential diagnosis of thyrotoxicosis with abnormal liver enzymes includes severe hyperthyroidism and thyroid storm caused by Graves’ disease as well as the thyrotoxic phase of a thyroiditis, usually caused by a virus such as coxsackievirus or, in this case, cytomegalovirus.

  • Cytomegalovirus appears to be a recently recognized causal agent for thyroiditis, both in immunosuppressed and immunocompetent patients.

  • Careful follow-up of thyroid function tests in patients with thyroiditis allows clinicians to determine if patients’ thyroid hormone secretion normalizes or if they remain hypothyroid.

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Wei Lin Tay Department of Endocrinology, Singapore General Hospital, Singapore, Singapore

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Wann Jia Loh Department of Endocrinology, Changi General Hospital, Singapore, Singapore

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Lianne Ai Ling Lee Department of Pathology, Sengkang Health, Singapore, Singapore

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Chiaw Ling Chng Department of Endocrinology, Singapore General Hospital, Singapore, Singapore

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Summary

We report a patient with Graves’ disease who remained persistently hyperthyroid after a total thyroidectomy and also developed de novo Graves’ ophthalmopathy 5 months after surgery. She was subsequently found to have a mature cystic teratoma containing struma ovarii after undergoing a total hysterectomy and salpingo-oophorectomy for an incidental ovarian lesion.

Learning points:

  • It is important to investigate for other causes of primary hyperthyroidism when thyrotoxicosis persists after total thyroidectomy.

  • TSH receptor antibody may persist after total thyroidectomy and may potentially contribute to the development of de novo Graves’ ophthalmopathy.

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Colin L Knight Department of Endocrinology and Diabetes, University Hospital Geelong, Geelong, Victoria, Australia

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Shamil D Cooray Department of Endocrinology and Diabetes, University Hospital Geelong, Geelong, Victoria, Australia

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Jaideep Kulkarni Department of Endocrinology and Diabetes, University Hospital Geelong, Geelong, Victoria, Australia

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Michael Borschmann Ear, Nose and Throat, Head and Neck Surgery, St. John of God Hospital, Geelong, Victoria, Australia
Director of Otolaryngology, University Hospital Geelong, Geelong, Victoria, Australia

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Mark Kotowicz Department of Endocrinology and Diabetes, University Hospital Geelong, Geelong, Victoria, Australia
Deakin University School of Medicine, Geelong, Victoria, Australia
Melbourne Clinical School-Western Campus, Department of Medicine, The University of Melbourne, St. Albans, Victoria, Australia

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A 51 year old man presented with sepsis in the setting of thioamide-induced agranulocytosis. Empiric broad-spectrum antibiotics was followed by directed narrow-spectrum antibiotics, and his neutrophil count recovered with support from granulocyte-colony stimulating factor (G-CSF) analogue transfusions. After a brief period of multi-modal therapy for nine days including potassium iodide (Lugol’s iodine), cholestyramine, propanolol and lithium to temper his persisting hyperthyroidism, a total thyroidectomy was performed while thyroid hormone levels remained at thyrotoxic levels. Postoperative recovery was uncomplicated and he was discharged home on thyroxine. There is limited available evidence to guide treatment in this unique cohort of patients who require prompt management to avert impending clinical deterioration. This case report summarises the successful emergent control of thyrotoxicosis in the setting of thioamide-induced agranulocytosis complicated by sepsis, and demonstrates the safe use of multi-modal pharmacological therapies in preparation for total thyroidectomy.

Learning points:

  • Thioamide-induced agranulocytosis is an uncommon but potentially life-threatening complication of which all prescribers and patients need to be aware.

  • A multi-modal preoperative pharmacological approach can be successful, even when thioamides are contraindicated, when needing to prepare a thyrotoxic patient for semi-urgent total thyroidectomy.

  • There is not enough evidence to confidently predict the safe timing when considering total thyroidectomy in this patient cohort, and therefore it should be undertaken when attempts have first been made to safely reduce thyroid hormone levels.

  • Thyroid storm is frequently cited as a potentially severe complication of thyroid surgery undertaken in thyrotoxic patients, although the evidence does not demonstrate this as a common occurrence.

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R D’Arcy Regional Centre for Endocrinology, Royal Victoria Hospital, Belfast, UK

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M McDonnell Regional Centre for Endocrinology, Royal Victoria Hospital, Belfast, UK

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K Spence Regional Centre for Endocrinology, Royal Victoria Hospital, Belfast, UK

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C H Courtney Regional Centre for Endocrinology, Royal Victoria Hospital, Belfast, UK

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Summary

A 42-year-old male presented with a one-week history of palpitations and sweating episodes. The only significant history was of longstanding idiopathic dilated cardiomyopathy. Initial ECG demonstrated a sinus tachycardia. Thyroid function testing, undertaken as part of the diagnostic workup, revealed an un-measureable thyroid-stimulating hormone (TSH) and free thyroxine (T4). Upon questioning the patient reported classical thyrotoxic symptoms over the preceding weeks. Given the persistence of symptoms free tri-iodothyronine (T3) was measured and found to be markedly elevated at 48.9 pmol/L (normal range: 3.1–6.8 pmol/L). No goitre or nodular disease was palpable in the neck. Historically there had never been any amiodarone usage. Radionucleotide thyroid uptake imaging (123I) demonstrated significantly reduced tracer uptake in the thyroid. Upon further questioning the patient reported purchasing a weight loss product online from India which supposedly contained sibutramine. He provided one of the tablets and laboratory analysis confirmed the presence of T3 in the tablet. Full symptomatic resolution and normalised thyroid function ensued upon discontinuation of the supplement.

Learning points:

  • Free tri-iodothyronine (T3) measurement may be useful in the presence of symptoms suggestive of thyrotoxicosis with discordant thyroid function tests.

  • Thyroid uptake scanning can be a useful aid to differentiating exogenous hormone exposure from endogenous hyperthyroidism.

  • Ingestion of thyroid hormone may be inadvertent in cases of exogenous thyrotoxicosis.

  • Medicines and supplements sourced online for weight loss may contain thyroxine (T4) or T3 and should be considered as a cause of unexplained exogenous hyperthyroidism.

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Guadalupe Vargas Endocrinology Service and Experimental Endocrinology Unit, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, IMSS, Mexico City, Mexico

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Lourdes-Josefina Balcazar-Hernandez Endocrinology Service and Experimental Endocrinology Unit, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, IMSS, Mexico City, Mexico

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Virgilio Melgar Neurological Center

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Roser-Montserrat Magriña-Mercado Endocrinology Service and Experimental Endocrinology Unit, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, IMSS, Mexico City, Mexico

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Baldomero Gonzalez Endocrinology Service and Experimental Endocrinology Unit, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, IMSS, Mexico City, Mexico

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Javier Baquera Pathology Department, American British Cowdray Hospital, Mexico City, Mexico

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Moisés Mercado Endocrinology Service and Experimental Endocrinology Unit, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, IMSS, Mexico City, Mexico
Neurological Center

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A 19-year-old woman with a history of isosexual precocious puberty and bilateral oophorectomy at age 10 years because of giant ovarian cysts, presents with headaches and mild symptoms and signs of hyperthyroidism. Hormonal evaluation revealed elevated FSH and LH levels in the postmenopausal range and free hyperthyroxinemia with an inappropriately normal TSH. Pituitary MRI showed a 2-cm macroadenoma with suprasellar extension. She underwent successful surgical resection of the pituitary tumor, which proved to be composed of two distinct populations of cells, each of them strongly immunoreactive for FSH and TSH, respectively. This mixed adenoma resulted in two different hormonal hypersecretion syndromes: the first one during childhood and consisting of central precocious puberty and ovarian hyperstimulation due to the excessive secretion of biologically active FSH and which was not investigated in detail and 10 years later, central hyperthyroidism due to inappropriate secretion of biologically active TSH. Although infrequent, two cases of isosexual central precocious puberty in girls due to biologically active FSH secreted by a pituitary adenoma have been previously reported in the literature. However, this is the first reported case of a mixed adenoma capable of secreting both, biologically active FSH and TSH.

Learning points:

  • Although functioning gonadotrophinomas are infrequent, they should be included in the differential diagnosis of isosexual central precocious puberty.

  • Some functioning gonadotrophinomas are mixed adenomas, secreting other biologically active hormones besides FSH, such as TSH.

  • Early recognition and appropriate treatment of these tumors by transsphenoidal surgery is crucial in order to avoid unnecessary therapeutic interventions that may irreversibly compromise gonadal function.

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Alfredo Di Cerbo Endocrinology, ‘Casa Sollievo della Sofferenza’, IRCCS, San Giovanni Rotondo, Foggia, Italy

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Federica Pezzuto Department of Medical, Oral and Biotechnological Sciences, Dental School, University ‘G. d’Annunzio’ of Chieti-Pescara, Chieti, Italy

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Alessandro Di Cerbo Department of Medical, Oral and Biotechnological Sciences, Dental School, University ‘G. d’Annunzio’ of Chieti-Pescara, Chieti, Italy

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Summary

Graves’ disease, the most common form of hyperthyroidism in iodine-replete countries, is associated with the presence of immunoglobulins G (IgGs) that are responsible for thyroid growth and hyperfunction. In this article, we report the unusual case of a patient with acromegaly and a severe form of Graves’ disease. Here, we address the issue concerning the role of growth hormone (GH) and insulin-like growth factor 1 (IGF1) in influencing thyroid function. Severity of Graves’ disease is exacerbated by coexistent acromegaly and both activity indexes and symptoms and signs of Graves’ disease improve after the surgical remission of acromegaly. We also discuss by which signaling pathways GH and IGF1 may play an integrating role in regulating the function of the immune system in Graves’ disease and synergize the stimulatory activity of Graves’ IgGs.

Learning points:

  • Clinical observations have demonstrated an increased prevalence of euthyroid and hyperthyroid goiters in patients with acromegaly.

  • The coexistence of acromegaly and Graves’ disease is a very unusual event, the prevalence being <1%.

  • Previous in vitro studies have showed that IGF1 synergizes the TSH-induced thyroid cell growth-activating pathways independent of TSH/cAMP/PKA cascade.

  • We report the first case of a severe form of Graves’ disease associated with acromegaly and show that surgical remission of acromegaly leads to a better control of symptoms of Graves’ disease.

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